PeriOperative ISchemic Evaluation-3 Trial: A Pilot Study (POISE-3)

PeriOperative ISchemic Evaluation-3 Trial: A Pilot Study (POISE-3)

A placebo-controlled, factorial trial to assess the impact of rosuvastatin and tranexamic acid (TXA) in patients undergoing noncardiac surgery who are at risk of a perioperative cardiovascular event.

Study Overview

• Status: Completed
• Conditions: Atherosclerotic Disease; Perioperative Bleeding
• Intervention / Treatment: Drug: Tranexamic Acid; Drug: Tranexamic Acid Placebo; Drug: Rosuvastatin or matching placebo

Detailed Description

The POISE-3 pilot is a randomized controlled trial of 100 patients with, or at risk of, atherosclerotic disease who are undergoing noncardiac surgery. Utilizing a partial factorial design, the POISE-3 pilot will determine the effect of rosuvastatin versus placebo and TXA versus placebo in the perioperative setting.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. undergoing noncardiac surgery
2. >45 years of age
3. expected to require at least an overnight hospital admission after surgery; AND
4. have a preoperative NT-pro-BNP measurement >100 ng/mL; OR

5. if a preoperative NT-pro-BNP measurement is not available, then the patient must fulfill 1 or more of the following 5 criteria:

   • history of coronary artery disease
   • history of peripheral vascular disease
   • history of stroke
   • undergoing major vascular surgery

   • have any 3 of the following 9 risk criteria:

     • undergoing major surgery
     • history of congestive heart failure
     • history of a transient ischemic attack
     • diabetic and currently taking an oral hypoglycemic agent or insulin
     • age >70 years
     • hypertension
     • serum creatinine > 175 umol/L (>2.0 mg/dl)
     • history of smoking within 2 years of surgery
     • undergoing emergent/urgent surgery

Exclusion Criteria:

1. planned use of systemic Tranexamic Acid during surgery
2. hypersensitivity or known allergy to TXA
3. creatinine clearance <30 mL/min (MDRD)
4. history of seizure disorder
5. history of venous thromboembolism
6. acute arterial thrombosis
7. no preoperative measurement of hemoglobin
8. subarachnoid hemorrhage within the past 30 days
9. hematuria caused by diseases of the renal parenchyma
10. previously enrolled in POISE-3 pilot trial
11. not consenting to participate in POISE-3 pilot trial prior to surgery

Patients meeting any of the following criteria will be excluded from the Rosuvastatin/Placebo arm:

1. preoperative treatment with a statin or a non statin lipid lowering drug or ciclosporin during the 48 hours before surgery
2. hypersensitivity or known allergy to Rosuvastatin
3. pre-disposed factors for myopathy or rhabdomyolysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tranexamic Acid vs. matching placebo; Tranexamic Acid 1g bolus with anesthesia induction followed by 1g bolus at the start of surgical closure.	Drug: Tranexamic Acid; Other Names: Cyklokapron; Drug: Tranexamic Acid Placebo
EXPERIMENTAL: Rosuvastatin vs. matching placebo; Rosuvastatin 20 mg orally or matching placebo once per day until 30 days after surgery	Drug: Rosuvastatin or matching placebo; Subjects who are not on a statin will also be randomized to Rosuvastatin or Rosuvastatin placebo. 40mg preoperatively, followed by 20mg postoperatively (4-6 hours after surgical close) and 20mg/day for 30 days postoperatively.; Other Names: Crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative intervention discontinuation	Interruption of the intervention longer than 24 hours within the first 10 days postoperatively, and longer than 48 hours from postoperative day 10 to 30.	Postoperative day 1 to 30.
Change in hemoglobin	Change in preoperative hemoglobin to the morning hemoglobin recorded on day 1 after surgery.	Postoperative day 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality		Postoperative day 30.
Non-fatal myocardial infarction		Postoperative day 30.
A composite of vascular mortality and non-fatal: myocardial infarction, stroke, cardiac arrest, pulmonary embolus, deep venous thrombosis, life threatening bleeding, major bleeding.	Event composite	Postoperative day 30.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcomes for Rosuvastatin assessed by Statin induced myopathy		Postoperative day 30.
Safety Outcomes for Tranexamic Acid assessed by Seizure, pulmonary emboli, deep venous thrombosis, vascular mortality	myocardial infarction, stroke, non-fatal cardiac arrest, and cardiac revascularization procedure.	Postoperative day 30.

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Hamilton Health Sciences Corporation; Population Health Research Institute
• Investigators: Study Chair: James Khan, MD, Hamilton Health Sciences Corporation

Publications and helpful links

General Publications

• Marcucci M, Duceppe E, Le Manach Y, Kearon C, Eikelboom JW, Pohl K, Vincent J, Darvish-Kazem S, Srinathan SK, Neary JDD, Parlow JL, Kurz A, Gross PL, Mrkobrada M, Balasubramanian K, Sessler DI, Devereaux PJ. Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial. Pilot Feasibility Stud. 2020 Jul 21;6:104. doi: 10.1186/s40814-020-00643-9. eCollection 2020.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (ACTUAL): October 1, 2015
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (ESTIMATE): September 11, 2015

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrin Modulating Agents; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Antifibrinolytic Agents; Hemostatics; Coagulants; Rosuvastatin Calcium; Tranexamic Acid
• Other Study ID Numbers: POISE3034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO